Published on November 11th, 2014 | by charlesriver50
Minipig Strains and the Emergence of the Göttingen Minipig
ICH guidelines require the use of two species in nonclinical studies for pharmaceuticals; one rodent and one nonrodent species. With many anatomical, physiological and functional similarities to humans, the miniature pig (minipig, Sus scrofa) has become a viable alternative nonrodent animal model in nonclinical safety testing.
While the minipig is subject to the same ethical and humane care concerns as other nonrodent species, its use in nonclinical safety testing appears to be more acceptable to the general public. In addition, there are many cases in which the minipig is considered the most appropriate model from a scientific perspective.
The strains of miniature swine available for nonclinical studies are the Göttingen minipig, Hanford minipig, Yucatan minipig and micropig, Troll minipig and Sinclair minipig.
The Göttingen minipig originated at the University of Göttingen (Germany) in the 1960s as the result of crossbreeding the Vietnamese swine, the Hormel or Minnesota miniature swine and the German-improved Landrace. Due to the Göttingen minipig’s small stature, relatively calm demeanor and suitability for most testing purposes, it has rapidly become the mainstay for nonclinical testing in miniature pigs.
Göttingen minipigs generally reach sexual maturity at an earlier age compared to standard nonrodent species used in drug safety studies, with boars reaching maturity as early as 3-4 months and some sows reaching maturity by 4-5 months. At the age that minipigs are commonly used in drug safety studies (~3-5 months) many will approach maturity by the end of 28-day studies and most will achieve complete maturity by the end of 13-week studies.
The Minipig in Nonclinical Safety Studies
Initially, minipigs were primarily used as the preferred large animal species for safety testing in the development of dermal pharmaceutical products. This was due to the fact that compared to other nonrodent species, the skin of the minipig more closely resembles that of humans in many respects, including sparse distribution of the hair coat, overall histological appearance, epidermal thickness, keratinocyte turnover time, xenobiotic metabolic activity, and similar dermal penetration rates for many chemicals. In addition to the dermal route of administration, minipigs are easily dosed via oral (gavage or capsule), intravenous and subcutaneous routes.
As minipigs were more frequently utilized, it was discovered that there were many cases which suggested that these animals could be suitable alternatives to the standard nonrodent species because of species-specific, dose-limiting toxicity to drugs of certain classes or drug vehicles. Examples of drug classes include cytotoxic anticancer drugs and nonsteroidal anti-inflammatory drugs (NSAIDs). Minipigs are also refractory to anaphylactoid responses following intravenous injections of certain vehicles (e.g. Tween 80 and Cremophor EL).
Relative to other nonrodent species, the greatest limitation of the minipig is perhaps its physical size, which in most cases requires greater quantities of test article, and poses technical challenges when handling older animals. Despite this potential drawback, the use of the minipig in nonclinical safety applications continues to increase every year. With greater characterization of the minipig model and ever-expanding historical control databases, the minipig is poised to replace standard nonrodent species in many pharmaceutical development programs.
- Bode, G. et al. The utility of the minipig as an animal model in regulatory toxicology. J. Pharmacol. Toxicol. Methods 62: 196–220, 2010.
- Ellegaard, L. et al. Welfare of the minipig with special reference to use in regulatory toxicology studies. J. Pharmacol. Toxicol. Methods 62: 167–183, 2010.
- Lehman, H. The minipig in general toxicology. Scand. J. Lab. Anim. Sci., Suppl. 1., Vol. 25: 59-62, 1998.
- Mortensen J.T. et al. The minipig in dermal toxicology. A Literature Review. Scand. J. Lab. Anim. Sci., Suppl. 1., Vol. 25: 77-83, 1998.
- Swindle, M.M. et al. Biology and Medicine of Swine. In: Laboratory Animal Medicine and Management, J.D. Reuter and M.A. Suckow (Eds.). International Veterinary Information Service, Ithaca, NY. 2003.
- Van der Laan, J.W. et al. Regulatory acceptability of the minipig in the development of pharmaceuticals, chemicals and other products. J. Pharmacol. Toxicol. Methods 62: 184–195, 2010.